LABORATORY DIAGNOSTICS OF DIABETES MELLITUS Epidemiology n About

LABORATORY DIAGNOSTICS OF DIABETES MELLITUS

Epidemiology n About 2 to 4 % of the world population is affected with DM n The disease is more common: - in persons after age 45 in obese individuals in certain ethnic groups in those with a positive family history of DM n In patients with type 1 DM, complications from end stage renal disease are major cause of death, whereas patients with type 2 diabetes are more likely to have macrovascular diseases leading to myocardial infarction and stroke as main causes of the death

Diabetes mellitus (DM) is endocrine – metabolic disease, which develops due to absolute or relative insulin insufficiency and characterized by chronic hyperglycemia, changes of different systems and organs of patient

Hormones of pancreatic gland Type of cells Quantity of cells (%) Secreted hormone Α 20 – 25 glucagon Β 75 – 80 insulin Δ 5 – 15 somatostatin G - gastrin РР 5 - 10 pancreatic polypeptide

Insulin n Molecular weight of this peptic substance is 6000. n It consists of 51 aminoacidic parts from 16 different aminoacids n The most important biologic stimulator of insulin secretion is glucose

The action of insulin n Insulin is an anabolic hormone (promotes the synthesis of carbohydrates, proteins, lipids and nucleic acids). The most important target organs for insulin action are: n the liver, muscles and adipocytes. n The brain (nervous tissue), retina, lens and blood cells are unresponsive to insulin. n It has no direct influence on kidney also

The action of insulin n Insulin is an anabolic hormone (promotes the synthesis of carbohydrates, proteins, lipids and nucleic acids). The most important target organs for insulin action are: n the liver, muscles and adipocytes. n The brain (nervous tissue), retina, lens and blood cells are unresponsive to insulin. n It has no direct influence on kidney also

The effects of insulin on carbohydrate metabolism n stimulation of glucose transport across muscle and adipose cell membranes; n regulation of hepatic glycogen synthesis; n inhibition of glucose formation – from glycogen (glycogenolysis) and – from aminoacid precursors (glyconeogenesis). n The result of these actions is a reduction in blood glucose concentration.

Protein metabolism: n the transfer of amino acids across plasma membranes; n stimulation of protein synthesis; n inhibition of proteolysis.

Lipid metabolism: n incorporation of fatty acids from circulating triglyceride into adipose triglyceride; n stimulation of lipid synthesis; n inhibition of lipolisis.

Nucleic acids metabolism: n stimulation of nucleic acid synthesis by stimulating the formation of adenosine triphosphate (ATP), DNA and RNF. Other effects: n stimulation of the intracellular flew of potassium, phosphate and magnesium in the heart; n inhibition of inotropic and chronoropic action (unrelated to hypoglycemia).

Pathogenesis of type 1 DM

Etiologic classification of DM (1999) I. Type 1 of DM (destruction of β-cells which mostly leads to absolute insulin insufficiency): n n autoimmune; idiopathic. II. Type 2 of DM (resistance to insulin and relative insulin insufficiency or defect of insulin secretion with or without resistance to insulin). III. Other specific types: n n n genetic defects of β-cells function; genetic defects of insulin action; pancreatic diseases (chronic pancreatitis; trauma, pancreatectomy; tumor of pancreatic gland; fibrocalculosis; hemochromatosis); endocrine disease (acromegaly, thyrotoxicosis, Cushing’s syndrome); drug exposures ; infections and others. IV. Gestation diabetes.

Degrees of severity of DM Mild Moderate Severe Fast serum glucose, mmol/l <8 8 - 14 > 14 Glucosuria, gr. /l < 20 (< 2 %) 20 – 40 (2 – 4 %) > 40 (4 %) Compensation can be achieved by diet oral hypoglycemic agents or insulin Chronic and acute complications only functional stages not last stages ketosis can occur last stages of chronic complications are present, ketosis is common

Pathogenetic and clinical difference of type I and type II DM N Signs Type 1 Type 2 1 Age Young (under 35) Old, middle 2 Beginning of disease Acute Gradual 3 Duration Labile Stable 4 Ketosis, ketoacidosis Often develops Rarely develops 5 Body weight Decreased or normal Obesity in 80 -90 % of patients

Pathogenetic and clinical difference of type I and type II DM N Signs Type 1 Type 2 6 Treatment Insulin, diet Diet, drugs, insulin 7 Degrees of severity Middle, hard Mild, middle, hard 8 Season of disease beginning Frequently autumn-winter period Absent 9 Connection with HBA-system Present Absent 10 Level of insulin and C-peptide Decreased or absent Frequently normal level

Pathogenetic and clinical difference of type I and type II DM N Signs Type 1 Type 2 11. Antibodies to β-cells Present in 80 -90 % of patients on first week, month Absent 12. Late complications Microangiopathies Macroangiopathies 13. Mortality Less than 10% More than 20% 14. Spreading 10 -20% 80 -90%

Pathophysiology of DM Defective polymorphonuclear function → infection ↑ Hyperglycemia → glucosurea → polyurea → dehydration Insulin lack ↓ Hyperosmolality Proteolysis → weight loss → muscle wasting → polyphagia Lipolysis → free fatty acid release → ketosis → acidosis

Sign Ischemic Temperature of the skin Decreased Color of the skin pallor or cyanotic Pulsation on peripheral decreased or vessels absent Edema Neuropatic normal or pink normal Sensibility Absent can be partly decreased or decreased normal absent Ulcers peripheral (distant) Gangrene Dry under pressure moist or the

n Oral glucose tolerance test (OGTT) Indications: n borderline fasting or post-prandial blood glucose n persistent glycosuria n glycosuria in pregnant women with a family history of diabetes mellitus and those who previously had large babies or unexplained fetal loss

Glucose tolerance test (GTT) Fasting serum glucose, mmol/l 2 hours after glucose loading, mmol/l Capillary blood Health 3, 3 – 5, 5 <7, 8 Impaired glucose tolerance 5, 6 – 6, 1 7, 8 – 11, 1 Diabetes mellitus > 6, 1 > 11, 1 Impaired fast glucose tolerance 5, 6 – 6, 1 < 7, 8

Screening for diabetes n n n n with typical symptoms of diabetes __ with a first-degree relative with diabetes __ who are members of a high risk ethnic group __ who are overweight (BMI ≥ 25. 0 kg/m²) __ who have delivered a baby >4. 5 kg or had GDM __ who are hypertensive (≥ 140/90 mm. Hg) __ with raised serum triglyceride and cholesterol levels __ who were previously found to have IGT or IFG

n The basic laboratory measures for screening are: n 1. Fasting capillary blood glucose n 2. Glucosuria n 3. Hb. A 1 c n 4. OGTT

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